PROJECT SUMMARY The sense of taste has evolved to detect nutrients and toxic substances in food and beverages--it is the sensory system that we rely on to make food choices. Taste dysfunction can substantially affect health: severe taste loss can lead to malnutrition, weight loss, and depression. Taste disorders can develop with various diseases, including many with underlying inflammation, such as infections and autoimmune diseases. The mechanisms of taste disorders associated with infections, autoimmune diseases, and chronic inflammatory diseases are poorly understood. Our recent research indicates that inflammation, characterized by induction of inflammatory cytokines, infiltration and activation of immune cells, may contribute to taste dysfunction. The goal of this research is to determine the molecular and cellular mechanisms of inflammation-triggered taste loss and its recovery and to explore treatment options to accelerate taste bud regeneration. The inflammatory cytokine interferon-? (IFN-?) is highly induced in taste epithelium in multiple disease models that show taste abnormalities. However, whether induction of IFN-? in the taste epithelium contributes to taste loss has not been determined. To directly test the role of IFN-? in taste loss, we have established transgenic mouse strains that allow selective induction of IFN-? in particular cell types in the taste epithelium: taste progenitor/stem cells, sweet and umami receptor cells, and sour receptor cells. Here, we propose to use these mouse models to determine the role of IFN-? in taste loss and to elucidate the molecular and cellular mechanisms that drive taste loss and taste bud regeneration. We will investigate the effects of IFN-? on taste bud cell renewal, cell death, taste pore structure, taste bud permeability, and immune cell trafficking in taste papillae. In addition, we will identify the molecular and cellular processes that are critical to taste bud regeneration following taste loss triggered by inflammation. Furthermore, we will determine whether exogenous growth factors can accelerate taste bud regeneration. This research will improve our understanding of the underlying mechanisms of taste loss and taste bud regeneration and shed new light on fundamental aspects of taste biology.